Mohsen Farsad

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkins disease (HD) or aggressive non-Hodgkins lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET+/CT− relapsed, as compared with zero out of 29 patients in the PET−/CT− subset. Among the 41 CT+ patients, 10 out of 11 (91%) who were PET+ relapsed, as compared with 0 out of 30 who were PET−. The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET+ and PET− subsets, respectively (P=0.00001). All five patients who were PET+/CT− underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET−/CT+ (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients

BACKGROUND A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

BackgroundMultiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients.AimAs MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM.MethodsTen patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions.ResultsFour patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8).ConclusionAccording to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

18F-FDG PET in mucosa-associated lymphoid tissue (MALT) lymphoma

To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 – 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma.

Role of 18F-dopa PET/CT imaging in the management of patients with 111In-pentetreotide negative GEP tumours.

PurposeTo assess whether 18F-dopa PET/CT is able to provide information relevant in changing the clinical management of patients with gastro-enteropancreatic (GEP) tumours where there is negative or inconclusive conventional radiological imaging (ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) and 111In-pentetreotide scintigraphy. Materials and methodsFrom January 2005 to October 2006, 84 patients with clinical and biochemical suspicion of GEP tumours were investigated by US and CT scans, MRI and 111In-pentetreotide scintigraphy. In 13/84 (15.4%) both conventional radiological imaging and 111In-pentetreotide scintigraphy provided negative or inconclusive findings, and patients were referred for 18F-dopa PET/CT imaging. Each patient received 5.3 MBq · kg−1 18F-dopa intravenously, and imaged 60 min later using a hybrid PET/CT scanner. Results18F-dopa PET/CT detected the primary tumour in all 13 patients (size range, 7–26 mm, mean, 18 mm; SUVmax range, 2.3–16.3, mean, 5.7) and further 12 unsuspected lesions (size range, 12–23 mm, mean 17; SUVmax range 2.8–12.7, mean 4.6). Confirmation of the PET/CT findings was obtained in all patients from histopathological analysis of tissue obtained after surgery and/or biopsy. All the 18F-dopa-positive primary lesions were confirmed as being the primary tumour at histology, whereas of the other 12 unsuspected 18F-dopa-positive lesions, 11 were found to be metastatic deposits and one due to unspecific inflammation (one false positive result). Notably, the results of 18F-dopa PET/CT imaging changed the clinical management in 11/13 patients (84%). ConclusionsOur preliminary results suggest that 18F-dopa PET/CT has a promising role in GEP patients with negative or inconclusive findings at conventional radiological imaging and 111In-pentetreotide scintigraphy. The findings were helpful in biopsy guidance and played a major role in changing the management of those patients.

Role of 18F-FDG PET for Evaluating Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.

Somatostatin receptor scintigraphy for bronchial carcinoid follow-up

Purpose: Somatostatin receptor scintigraphy (SRS) has been used to diagnose bronchial carcinoids (BC) and is a valuable tool for accurate staging of BC. The aim of this study was to evaluate the role of SRS in restaging BC and following patients after treatment. Methods: Thirty‐one patients (18 male, 13 female) with confirmed BC who were referred during the last 7 years were included. Patients were examined via chest radiograph (12 studies), chest or abdominal computed tomography (CT; 28 scans), chest magnetic resonance imaging (2 scans), and liver ultrasound (5 scans). Results: Overall, in 22 patients (71%), SRS confirmed the data obtained by other diagnostic procedures (16 negative and 6 positive findings). In 6 patients, SRS showed focal lesions not previously demonstrated. In 2 patients, SRS resolved uncertain findings of CT. In 1 patient, SRS showed fewer lesions compared with CT. In 8 of 31 patients, important diagnostic information obtained by SRS was not revealed by any other imaging procedure. Conclusion: Our results indicate that SRS is a reliable, noninvasive method that could be considered the principal follow‐up procedure in patients with BC.

11C-methionine PET/CT in 99mTc-sestamibi-negative hyperparathyroidism in patients with renal failure on chronic haemodialysis

PurposeScintigraphic localisation of parathyroid glands is often unsuccessful in patients with renal failure on chronic haemodialysis who have secondary hyperparathyroidism (HPT). The purpose of this study was to investigate the use of 11C-methionine PET/CT to detect hyperfunctioning parathyroid glands in patients with renal failure on chronic haemodialysis who had 99mTc-sestamibi-negative HPT.Methods11C-methionine PET/CT was performed in 18 patients (11 women and 7 men, aged 42–79 years; mean age 57.8 years) on haemodialysis for renal failure (2–14 years’ duration), with normo-, hypo- or hypercalcaemia and HPT not localised by either dual-tracer 99mTc-pertechnetate/99mTc-sestamibi subtraction scans or dual-phase 99mTc-sestamibi scans.ResultsIn three of ten patients with normo- or hypocalcaemic HPT there was increased 11C-methionine accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed increased uptake: in five of these patients increased 11C-methionine accumulation was present in one gland, while in two it was demonstrated in two glands. All patients also had high-resolution ultrasound of the neck and were treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the four glands. Regardless of their size, all glands with abnormal 11C-methionine parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia. All patients developed post-parathyroidectomy hypoparathyroidism and one patient with normocalcaemic HPT relapsed 8 months after surgery.ConclusionThese data suggest that 11C-methionine PET/CT may be used to identify hyperfunctioning parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when conventional 99mTc-sestamibi imaging is non-localising.

11C/ 18F-choline PET or 11C/18F-acetate PET in prostate cancer: may a choice be recommended?

Dear Sir, Prostate cancer is one of the most common cancers and is the second leading cause of death from malignancy among US men [1]. The diagnostic flow chart, however, presents some issues during the whole disease history, in particular in the identification of the primary cancer, lymph node staging before treatment and detection of cancer relapse (local or metastatic) in the event of an increase in the serum PSA level. It is well known that the sensitivity of transrectal ultrasound (TRUS)-guided biopsy is reduced for patients with large prostates (the false negative rate is about 10–30%) and for tumours located in the apex, in the anterior prostate or in the lateral prostate [2–4]. Therefore, iterative biopsies are frequently required before a cancer focus is detected, with a resultant loss of time and increase in morbidity. Lymph node metastases are found in only 10–30% of high-risk prostate cancer patients [5]; conventional imaging techniques such as contrast-enhanced computed tomography (ceCT), magnetic resonance imaging (MRI) and ultrasound (US) do not play a significant role in their detection (these diagnostic modalities are sensitive for the detection of enlarged nodes but they are unspecific), and surgical dissection of pelvic lymph nodes remains the gold standard procedure. In patients treated for prostate cancer and presenting with a rising PSA, the localisation of the site of disease relapse is very important as the therapeutic approach differs according to whether there is local or localised relapse (therapy with a curative intent) or disseminated disease (systemic therapy). Sometimes, conventional imaging techniques (ceCT, MRI, US and bone scintigraphy) do not detect the site of disease relapse (in particular, the identification of lymph node metastases and local recurrence may be very problematic, especially after surgery or radiation therapy), leading to an inappropriate treatment choice. Considering these issues, there is clearly a need for a new diagnostic tool. After observing that FDG-PET is insufficiently sensitive in this field, in 1998 Hara and coworkers [6] introduced C-choline PET for the evaluation of prostate cancer patients. The uptake mechanism of C-choline by cancer cells is related to the increased proliferative activity of tumoural cells, although it is not related to Ki67 [7]. In fact, choline is one of the components of phosphatidylcholine, an essential element of phospholipids present in the cell membrane, whose synthesis is up-regulated in cancer. C-choline PET was proved to play a significant diagnostic role by several authors [8–10], in particular for the detection of cancer relapse sites. In fact, the uptake of C-choline in prostate cancer cells is high, and the renal excretion is low, increasing the accuracy of evaluation of the pelvis. The use of C-choline PET for the diagnosis of intraprostatic cancer and for lymph node staging has not been subjected to detailed study, and further literature reports are necessary since discordant results have been described [11–13]. Despite positive results, C-choline has the great disadvantage of having a very short half-life (20 min) Eur J Nucl Med Mol Imaging (2007) 34:1704–1705 DOI 10.1007/s00259-007-0491-5

Short Communication: 18F-FDG PET Early After Radiotherapy in Lymphoma Patients

OBJECTIVE The aim of this study was to evaluate the rate of postactinic inflammatory alterations that could lead to false-positive results in FDG-PET images, in a group of lymphoma patients studied with positron emission tomography (PET) early after the end of radiation therapy. MATERIALS AND METHODS Sixteen (16) consecutive patients were referred to our center for malignant lymphoma; 14 of 16 patients had a mediastinal bulky mass at diagnosis. Each patient underwent chemotherapy and then radiotherapy (RT): for clinical reasons, shortly after RT (range, 25-56 days; mean, 38.7 days) a FDG PET scan was required to evaluate the effect of therapy. We intravenously injected 370 MBq of 18F-FDG, and after 60-90 minutes we recorded images. RESULTS Despite a relatively short time after RT, there was no pathological tracer uptake in 13 of 16 patients. In 3 cases, a mild increase in FDG uptake was observed, but no findings which would lead to a false-positive diagnosis. In 2 of 3 cases, postactinic pneumopathy was diagnosed (PET scan performed 51 and 52 days after RT); while in 1 patient, soft-tissue inflammation was present (PET scan performed 42 days after RT). CONCLUSION Our data indicates that the rate of postactinic PET inflammatory alterations in lymphoma patients is not very high and appear to be not strictly linked to the elapsed time since the end of RT treatment.